Total soluble and endogenous secretory receptor for advanced glycation end products as predictive biomarkers of coronary heart disease risk in patients with type 2 Diabetes : an analysis from the CARDS trial. / Colhoun, Helen M.; Betteridge, D. John; Durrington, Paul; Hitman, Graham; Neil, Andrew; Livingstone, Shona; Charlton-Menys, Valentine; Bao, Weihang; DeMicco, David A.; Preston, Gregory M.; Deshmukh, Harshal; Tan, Kathryn; Fuller, John H.
In: Diabetes, Vol. 60, No. 9, 09.2011, p. 2379-2385.Research output: Contribution to journal › Article
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TY - JOUR
T1 - Total soluble and endogenous secretory receptor for advanced glycation end products as predictive biomarkers of coronary heart disease risk in patients with type 2 Diabetes
T2 - an analysis from the CARDS trial
A1 - Colhoun,Helen M.
A1 - Betteridge,D. John
A1 - Durrington,Paul
A1 - Hitman,Graham
A1 - Neil,Andrew
A1 - Livingstone,Shona
A1 - Charlton-Menys,Valentine
A1 - Bao,Weihang
A1 - DeMicco,David A.
A1 - Preston,Gregory M.
A1 - Deshmukh,Harshal
A1 - Tan,Kathryn
A1 - Fuller,John H.
AU - Colhoun,Helen M.
AU - Betteridge,D. John
AU - Durrington,Paul
AU - Hitman,Graham
AU - Neil,Andrew
AU - Livingstone,Shona
AU - Charlton-Menys,Valentine
AU - Bao,Weihang
AU - DeMicco,David A.
AU - Preston,Gregory M.
AU - Deshmukh,Harshal
AU - Tan,Kathryn
AU - Fuller,John H.
PY - 2011/9
Y1 - 2011/9
N2 - <p>OBJECTIVE-Circulating levels of soluble receptor for advanced glycation end products (sRAGE) likely comprise both a secreted isoforrn (esRAGE) and wild-type RAGE cleaved from the cell membrane. Both sRAGE and esRAGE have been proposed as biomarkers of cardiovascular disease (CVD), but prospective data are limited. We examined the relationship of sRAGE and esRAGE to incident coronary heart disease (CHD) and stroke in type 2 diabetic patients followed for 3.9 years in a trial of atorvastatin: the Collaborative Atorvastatin Diabetes Study (CARDS).</p><p>RESEARCH DESIGN AND METHODS-We used a nested case-control design sampling all incident cases of CVD with available plasma and randomly selecting three control subjects, who were free of CVD throughout follow-up, per case. Analysis was by Cox regression with adjustment for treatment allocation and relevant covariates.</p><p>RESULTS-sRAGE and esRAGE were strongly correlated (rho = 0.88) and were both higher in those with lower BMI (P < 0.001), higher adiponectin (P < 0.001), lower estimated glomerular filtration rate (P = 0.009), and white ethnicity (P < 0.001). Both sRAGE and esRAGE were associated with incident CHD events, independently of treatment allocation and the above factors; hazard ratio (HR) = 1.74 (95% CI 1.25-2.41; P = 0.002) for a doubling of the sRAGE level; HR = 1.45 (1.11-1.89; P = 0.006) for a doubling of the esRAGE level. There was no significant association with stroke; HR for sRAGE = 0.66 (0.38-1.14). Atorvastatin, 10 mg daily, did not alter sRAGE.</p><p>CONCLUSIONS-Higher levels of sRAGE and esRAGE are associated with incident CHD but not stroke in type 2 diabetes. Diabetes 60:2379-2385, 2011</p>
AB - <p>OBJECTIVE-Circulating levels of soluble receptor for advanced glycation end products (sRAGE) likely comprise both a secreted isoforrn (esRAGE) and wild-type RAGE cleaved from the cell membrane. Both sRAGE and esRAGE have been proposed as biomarkers of cardiovascular disease (CVD), but prospective data are limited. We examined the relationship of sRAGE and esRAGE to incident coronary heart disease (CHD) and stroke in type 2 diabetic patients followed for 3.9 years in a trial of atorvastatin: the Collaborative Atorvastatin Diabetes Study (CARDS).</p><p>RESEARCH DESIGN AND METHODS-We used a nested case-control design sampling all incident cases of CVD with available plasma and randomly selecting three control subjects, who were free of CVD throughout follow-up, per case. Analysis was by Cox regression with adjustment for treatment allocation and relevant covariates.</p><p>RESULTS-sRAGE and esRAGE were strongly correlated (rho = 0.88) and were both higher in those with lower BMI (P < 0.001), higher adiponectin (P < 0.001), lower estimated glomerular filtration rate (P = 0.009), and white ethnicity (P < 0.001). Both sRAGE and esRAGE were associated with incident CHD events, independently of treatment allocation and the above factors; hazard ratio (HR) = 1.74 (95% CI 1.25-2.41; P = 0.002) for a doubling of the sRAGE level; HR = 1.45 (1.11-1.89; P = 0.006) for a doubling of the esRAGE level. There was no significant association with stroke; HR for sRAGE = 0.66 (0.38-1.14). Atorvastatin, 10 mg daily, did not alter sRAGE.</p><p>CONCLUSIONS-Higher levels of sRAGE and esRAGE are associated with incident CHD but not stroke in type 2 diabetes. Diabetes 60:2379-2385, 2011</p>
KW - Cardiovascular disease
KW - Endproducts rage
KW - Association
KW - Atherosclerosis
KW - Complications
KW - Failure
KW - Level
KW - Srage
KW - Gene
KW - Form
U2 - 10.2337/db11-0291
DO - 10.2337/db11-0291
M1 - Article
JO - Diabetes
JF - Diabetes
SN - 0012-1797
IS - 9
VL - 60
SP - 2379
EP - 2385
ER -